RNA interference (RNAi) represents a platform of tremendous potential in the field of gene therapy. For therapeutics, a specific small interfering RNA (siRNA) is delivered into cells for the selective knock down of the encoded protein's expression. However, to fully realize the potential of siRNA therapeutics, safe and efficient delivery reagents must be developed. Recently in the Guan lab we have developed a dendritic peptide terminated bolaamphiphile system that can successfully deliver siRNA and knockdown protein expression. However, to increase clinical applications of the peptide bolaamphiphile, we must increase serum stability, biocompatibility, and systemic delivery. To address these issues I propose to synthesize a library of saccharide-functionalized bolaamphiphiles. Saccharide functionalization will increase serum stability by shielding the positive surface charge of the siRNA-polymer assembly, increase biocompatibility through reducing the membrane disruption by free amines, and finally will increase systemic delivery through lectin-saccharide interactions. I will fully investigate the self-assembly, biocompatibility, knockdown, and efficacy of this syste using similar methods developed in our lab to test related peptide bolaamphiphile system. Initial studies completed by myself have allowed for the creation of a mannose-functionalized bola amphiphile that has shown promising activity (88% knockdown of the target gene in serum). Successful completion of the proposed study will result in a new highly efficient siRNA delivery system, enabling further in vivo studies with collaborators which could lead to the successful treatment of several diseases including cancers, neurodegenerative disorders, and diabetes.